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    Clinical Trial Results:
    A 52-Week Phase 3 Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study to Assess the Efficacy, Safety and Tolerability of PF-04950615 in Subjects With Primary Hyperlipidemia or Mixed Dyslipidemia at Risk of Cardiovascular Events

    Summary
    EudraCT number
    2014-000478-20
    Trial protocol
    FI   GB   SE   CZ   NL   PL  
    Global end of trial date
    10 Jul 2017

    Results information
    Results version number
    v2(current)
    This version publication date
    22 Jul 2018
    First version publication date
    09 Jul 2017
    Other versions
    v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    B1481045
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02100514
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Pfizer, Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    02 Mar 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    10 Jul 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate a superior low-density lipoprotein cholesterol (LDL-C) lowering effect of Bococizumab (PF-04950615) 150 milligram (mg) administered by the subcutaneous (SC) route every 2 weeks (Q2W) compared to placebo, in subjects with primary hyperlipidemia or mixed dyslipidemia at high or very high risk for cardiovascular events receiving statin therapy and whose LDL-C is greater or equal to (>=) 100 milligram per deciliter (mg/dL) (2.59 millimole per liter [mmol/L]).
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    28 Oct 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 79
    Country: Number of subjects enrolled
    Czech Republic: 35
    Country: Number of subjects enrolled
    Finland: 3
    Country: Number of subjects enrolled
    Korea, Republic of: 6
    Country: Number of subjects enrolled
    Netherlands: 38
    Country: Number of subjects enrolled
    Norway: 17
    Country: Number of subjects enrolled
    Poland: 71
    Country: Number of subjects enrolled
    Puerto Rico: 7
    Country: Number of subjects enrolled
    Singapore: 6
    Country: Number of subjects enrolled
    Sweden: 14
    Country: Number of subjects enrolled
    United Kingdom: 24
    Country: Number of subjects enrolled
    United States: 446
    Worldwide total number of subjects
    746
    EEA total number of subjects
    202
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    429
    From 65 to 84 years
    315
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    This study was conducted at multiple sites from 28 October 2014 to 15 July 2016 for the Treatment Period and up to 10 July 2017 for the Extension Period.

    Period 1
    Period 1 title
    Treatment Period
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Investigator, Carer, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Treatment Period: Placebo
    Arm description
    Subjects received placebo matched to Bococizumab (PF-­04950615) subcutaneous injection once every 2 weeks up to Week 52. Subjects were followed up to Week 58.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks over a period of 52 weeks.

    Arm title
    Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Arm description
    Subjects received Bococizumab (PF­-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Subjects were followed up to Week 58.
    Arm type
    Experimental

    Investigational medicinal product name
    Bococizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received Bococizumab (PF-04950615) 150 mg subcutaneous injection once every 2 weeks over a period of 52 weeks.

    Number of subjects in period 1
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Started
    247
    499
    Completed
    218
    425
    Not completed
    29
    74
         Death
    2
    2
         Protocol deviation
    1
    1
         Adverse event
    -
    5
         Did Not Meet Entrance Criteria
    -
    1
         Unspecified
    9
    11
         Consent withdrawn by subject
    12
    37
         Lost to follow-up
    5
    17
    Period 2
    Period 2 title
    Extension Period
    Is this the baseline period?
    No
    Allocation method
    Non-randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Extension Period: Placebo
    Arm description
    Subjects randomized to Placebo arm in treatment period and consented for extension period after Week 58 follow-up visit, were followed for serious adverse events (SAEs) and concomitant medications up to Week 110.
    Arm type
    No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    Extension Period: Bococizumab ADA positive
    Arm description
    Subjects randomized to Bococizumab in treatment period were classified as either ADA positive or ADA negative based on their ADA assessment at Week 58 follow-up visit. In extension period, subjects who were ADA positive and consented for extension period were assessed for ADA and LDL-C direct measurement until ADA titers were no longer detectable or had returned to baseline titer (less than or equal to 1.58 [log2] units above a positive baseline titer) or until Week 110 along with SAEs and concomitant medication, from Week 58 follow up visit to Week 110.
    Arm type
    No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    Extension Period: Bococizumab ADA negative
    Arm description
    Subjects randomized to Bococizumab in treatment period were classified as either ADA positive or ADA negative based on their Week 58 follow-up ADA assessment. Subjects who were ADA negative and consented for extension period were followed for SAEs and concomitant medication, from Week 58 follow up visit to Week 110.
    Arm type
    No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 2 [1]
    Extension Period: Placebo Extension Period: Bococizumab ADA positive Extension Period: Bococizumab ADA negative
    Started
    44
    33
    56
    Completed
    42
    33
    56
    Not completed
    2
    0
    0
         Consent withdrawn by subject
    2
    -
    -
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Only subjects who consented for the extension period were followed in the extension period.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Treatment Period: Placebo
    Reporting group description
    Subjects received placebo matched to Bococizumab (PF-­04950615) subcutaneous injection once every 2 weeks up to Week 52. Subjects were followed up to Week 58.

    Reporting group title
    Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Reporting group description
    Subjects received Bococizumab (PF­-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Subjects were followed up to Week 58.

    Reporting group values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg Total
    Number of subjects
    247 499 746
    Age categorical
    Units: Subjects
        In utero
    0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0
        Newborns (0-27 days)
    0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0
        Children (2-11 years)
    0 0 0
        Adolescents (12-17 years)
    0 0 0
        Adults (18-64 years)
    144 285 429
        From 65-84 years
    102 213 315
        85 years and over
    1 1 2
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    61.7 ± 10.0 61.5 ± 9.9 -
    Gender, Male/Female
    Units: Subjects
        Female
    107 223 330
        Male
    140 276 416

    End points

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    End points reporting groups
    Reporting group title
    Treatment Period: Placebo
    Reporting group description
    Subjects received placebo matched to Bococizumab (PF-­04950615) subcutaneous injection once every 2 weeks up to Week 52. Subjects were followed up to Week 58.

    Reporting group title
    Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Reporting group description
    Subjects received Bococizumab (PF­-04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Subjects were followed up to Week 58.
    Reporting group title
    Extension Period: Placebo
    Reporting group description
    Subjects randomized to Placebo arm in treatment period and consented for extension period after Week 58 follow-up visit, were followed for serious adverse events (SAEs) and concomitant medications up to Week 110.

    Reporting group title
    Extension Period: Bococizumab ADA positive
    Reporting group description
    Subjects randomized to Bococizumab in treatment period were classified as either ADA positive or ADA negative based on their ADA assessment at Week 58 follow-up visit. In extension period, subjects who were ADA positive and consented for extension period were assessed for ADA and LDL-C direct measurement until ADA titers were no longer detectable or had returned to baseline titer (less than or equal to 1.58 [log2] units above a positive baseline titer) or until Week 110 along with SAEs and concomitant medication, from Week 58 follow up visit to Week 110.

    Reporting group title
    Extension Period: Bococizumab ADA negative
    Reporting group description
    Subjects randomized to Bococizumab in treatment period were classified as either ADA positive or ADA negative based on their Week 58 follow-up ADA assessment. Subjects who were ADA negative and consented for extension period were followed for SAEs and concomitant medication, from Week 58 follow up visit to Week 110.

    Primary: Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12

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    End point title
    Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
    End point description
    Full analysis set (FAS) included all subjects who were randomized. Here, "Number of subjects analyzed (N)" signifies number of subjects who were evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Baseline, Week 12
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    235
    468
    Units: percent change
        arithmetic mean (standard deviation)
    -0.8 ± 17.61
    -50.8 ± 29.81
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Least square (LS) mean difference and associated 95% confidence interval (CI), and p-value were derived from an mixed effect model repeat measurement (MMRM) model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    703
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    MMRM
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -49.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -54
         upper limit
    -45.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.09

    Secondary: Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52

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    End point title
    Percent Change From Baseline in Fasting Total Cholesterol (TC) at Week 12, 24 and 52
    End point description
    FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, 24, 52
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    247
    499
    Units: percent change
    arithmetic mean (standard deviation)
        Week 12 (n =236, 469)
    -2.2 ± 13.41
    -35.4 ± 20.93
        Week 24 (n =237, 463)
    -3.1 ± 15.79
    -32.9 ± 23.06
        Week 52 (n =221, 425)
    -5.0 ± 17.22
    -29.0 ± 22.08
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 12: LS mean difference and associated 95% CI and p-value were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    MMRM
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -33.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -36.1
         upper limit
    -30.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.48
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 24: LS mean difference and associated 95% CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -29.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -32.8
         upper limit
    -26.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.66
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 52: LS mean difference and associated 95% CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -23.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -27
         upper limit
    -20.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.65

    Secondary: Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52

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    End point title
    Percent Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12, 24 and 52
    End point description
    FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, 24, 52
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    247
    499
    Units: percent change
    arithmetic mean (standard deviation)
        Week 12 (n =234, 467)
    -0.6 ± 16.70
    -46.5 ± 28.87
        Week 24 (n =236, 461)
    -2.1 ± 18.66
    -43.5 ± 32.26
        Week 52 (n =221, 425)
    -4.4 ± 20.77
    -37.3 ± 29.59
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 12: LS mean difference and associated 95% CI, and p-value were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    MMRM
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -45.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -49.6
         upper limit
    -41.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.04
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 24: LS mean difference and associated 95% CI, were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -40.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -45.3
         upper limit
    -36.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.26
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 52: LS mean difference and associated 95% CI, were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -32.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -36.7
         upper limit
    -28.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.17

    Secondary: Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (non HDL-C) at Week 12, 24 and 52

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    End point title
    Percent Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (non HDL-C) at Week 12, 24 and 52
    End point description
    FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, 24, 52
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    247
    499
    Units: percent change
    arithmetic mean (standard deviation)
        Week 12 (n =236, 469)
    -2.6 ± 17.57
    -47.6 ± 28.36
        Week 24(n =237, 463)
    -3.8 ± 20.63
    -44.7 ± 30.83
        Week 52 (n =221, 425)
    -6.4 ± 22.70
    -39.5 ± 29.36
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 12: LS mean difference and associated 95% CI and p-value were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    MMRM
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -44.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -48.8
         upper limit
    -41
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.99
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -40.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -44.8
         upper limit
    -36.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.21
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -32.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -37
         upper limit
    -28.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.2

    Secondary: Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Less Than (<) 200 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52

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    End point title
    Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Less Than (<) 200 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52
    End point description
    A subset of FAS included all participants who were randomized and had TG <200 mg/dL at pre-randomization. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, 24, 52
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    164
    331
    Units: percent change
    arithmetic mean (standard deviation)
        Week 12 (n =158, 313)
    0.5 ± 16.61
    -51.1 ± 30.43
        Week 24 (n =159, 311)
    -1.6 ± 21.68
    -48.4 ± 33.67
        Week 52 (n =148, 292)
    -4.2 ± 24.11
    -42.2 ± 33.75
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 12: LS mean difference and associated 95% CI and p-value were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    495
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    MMRM
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -51.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -56.7
         upper limit
    -46.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.59
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    495
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -46.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -52.2
         upper limit
    -40.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.94
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    495
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -37.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -43.3
         upper limit
    -31.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.03

    Secondary: Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52

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    End point title
    Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52
    End point description
    A subset of FAS included all participants who were randomized and had TG >=200 mg/dL at pre-randomization. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, 24, 52
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    83
    168
    Units: percent change
    arithmetic mean (standard deviation)
        Week 12 (n =77,155)
    -3.4 ± 19.34
    -50.1 ± 28.62
        Week 24 (n =77,150)
    -5.7 ± 21.67
    -45.8 ± 33.13
        Week 52 (n =74,133)
    -5.7 ± 23.78
    -40.9 ± 30.25
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 12: LS mean difference and associated 95% CI and p-value were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    251
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    MMRM
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -46.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -53.7
         upper limit
    -39.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.59
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 24: LS mean difference and associated 95% CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    251
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -39.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -47.9
         upper limit
    -31.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.12
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 52: LS mean difference and associated 95% CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    251
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -33.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -41.3
         upper limit
    -25.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.02

    Secondary: Percent Change From Baseline in Fasting Lipoprotein (A) (Lp[A]) at Week 12, 24 and 52

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    End point title
    Percent Change From Baseline in Fasting Lipoprotein (A) (Lp[A]) at Week 12, 24 and 52
    End point description
    FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, 24, 52
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    247
    499
    Units: percent change
    arithmetic mean (standard deviation)
        Week 12 (n =235, 469)
    4.9 ± 54.24
    -25.7 ± 29.45
        Week 24 (n =235, 463)
    5.9 ± 50.52
    -21.3 ± 34.42
        Week 52 (n =221, 425)
    27.9 ± 374.64
    -21.5 ± 32.61
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 12: LS mean difference and associated 95% CI and p-value were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    MMRM
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -30.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -36.9
         upper limit
    -24.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.14
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -27.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -33.9
         upper limit
    -21.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.23
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -49.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -85.2
         upper limit
    -13.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    18.27

    Secondary: Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52

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    End point title
    Percent Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52
    End point description
    FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, 24, 52
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    247
    499
    Units: percent change
    arithmetic mean (standard deviation)
        Week 12 (n =236, 469)
    0.6 ± 13.93
    6.3 ± 13.86
        Week 24 (n =237, 463)
    0.6 ± 14.88
    6.3 ± 14.49
        Week 52 (n =221, 425)
    0.7 ± 14.24
    7.0 ± 15.60
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 12: LS mean difference and associated 95% CI and p-value were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    MMRM
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    5.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.4
         upper limit
    7.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.06
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    5.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.2
         upper limit
    7.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.14
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.6
         upper limit
    8.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.2

    Secondary: Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24 and 52: Treatment Period

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    End point title
    Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 24 and 52: Treatment Period
    End point description
    FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24, 52
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    247
    499
    Units: percent change
    arithmetic mean (standard deviation)
        Week 24 (n =236, 461)
    -2.9 ± 21.72
    -47.5 ± 33.48
        Week 52 (n =222, 425)
    -4.7 ± 23.96
    -41.8 ± 32.67
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -44.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -48.8
         upper limit
    -39.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.39
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -36.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -40.9
         upper limit
    -31.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.42

    Secondary: Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52

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    End point title
    Percent Change From Baseline in Fasting Triglycerides (TG) at Week 12, 24 and 52
    End point description
    FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, 24, 52
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    247
    499
    Units: percent change
    arithmetic mean (standard deviation)
        Week 12 (n =236, 469)
    -6.2 ± 32.92
    -16.2 ± 32.86
        Week 24 (n =237, 463)
    -8.9 ± 35.60
    -18.2 ± 65.13
        Week 52 (n =221, 425)
    -8.0 ± 41.46
    -15.8 ± 35.57
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 12: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -10.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -15.1
         upper limit
    -5.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.55
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -17.9
         upper limit
    -0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.5
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -8.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -14.1
         upper limit
    -2.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.04

    Secondary: Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52

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    End point title
    Percent Change From Baseline in Fasting Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52
    End point description
    FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, 24, 52
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    247
    499
    Units: percent change
    arithmetic mean (standard deviation)
        Week 12 (n =236, 468)
    -0.9 ± 11.09
    3.4 ± 11.43
        Week 24 (n =236, 461)
    -1.6 ± 10.81
    2.5 ± 11.61
        Week 52 (n =221, 425)
    -1.0 ± 13.12
    3.4 ± 11.77
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 12: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    4.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.5
         upper limit
    5.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.85
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    3.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.2
         upper limit
    5.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.86
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    4.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.4
         upper limit
    6.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.97

    Secondary: Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52

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    End point title
    Percent Change From Baseline in Fasting Apolipoprotein A-II (ApoA-II) at Week 12, 24 and 52
    End point description
    FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, 24, 52
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    247
    499
    Units: percent change
    arithmetic mean (standard deviation)
        Week 12 (n =235, 468)
    2.0 ± 11.94
    3.0 ± 11.94
        Week 24 (n =233, 462)
    2.6 ± 12.12
    3.7 ± 14.12
        Week 52 (n =220, 423)
    0.7 ± 12.46
    1.9 ± 12.22
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 12: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    1.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.7
         upper limit
    2.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.9
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    0.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    2.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.95
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.1
         upper limit
    3
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.04

    Secondary: Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52

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    End point title
    Percent Change From Baseline in Fasting Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 12, 24 and 52
    End point description
    FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, 24, 52
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    247
    499
    Units: percent change
    arithmetic mean (standard deviation)
        Week 12 (n =236, 469)
    -6.2 ± 32.92
    -16.2 ± 32.86
        Week 24 (n =237, 463)
    -8.9 ± 35.60
    -18.2 ± 65.13
        Week 52 (n =221, 425)
    -8.0 ± 41.46
    -15.8 ± 35.57
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 12: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -10.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -15.1
         upper limit
    -5.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.55
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -17.9
         upper limit
    -0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.5
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -8.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -14.1
         upper limit
    -2.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.04

    Secondary: Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Less Than (<) 200 Milligram per Deciliter (mg/dL) at Week 12

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    End point title
    Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Less Than (<) 200 Milligram per Deciliter (mg/dL) at Week 12
    End point description
    A subset of FAS included all participants who were randomized and had TG <200 mg/dL at pre-randomization. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    164
    331
    Units: mg/dL
    arithmetic mean (standard deviation)
        Baseline (n =164, 331)
    130.1 ± 25.22
    130.2 ± 28.72
        Change at Week 12 (n =158, 313)
    -0.5 ± 22.37
    -67.3 ± 40.14
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    495
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -66.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -73
         upper limit
    -60.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.18

    Secondary: Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram per Deciliter (mg/dL) at Week 12

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    End point title
    Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) by Triglycerides Cut-off of Greater Than or Equal to (>=) 200 Milligram per Deciliter (mg/dL) at Week 12
    End point description
    A subset of FAS included all participants who were randomized and had TG >=200 mg/dL at pre-randomization. Here,"n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    83
    168
    Units: mg/dL
    arithmetic mean (standard deviation)
        Baseline (n =83, 168)
    143.7 ± 35.49
    147.2 ± 39.48
        Change at Week 12 (n =77, 155)
    -6.6 ± 29.61
    -74.1 ± 48.04
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction and geographical region. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    251
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -66.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -76.7
         upper limit
    -55.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.4

    Secondary: Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12

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    End point title
    Absolute Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
    End point description
    FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    247
    499
    Units: mg/dL
    arithmetic mean (standard deviation)
        Baseline (n =247, 499)
    134.7 ± 29.71
    135.9 ± 33.67
        Change at Week 12 (n =235, 468)
    -2.5 ± 25.07
    -69.6 ± 42.98
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -66.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -72
         upper limit
    -61.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.77

    Secondary: Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12

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    End point title
    Absolute Change From Baseline in Fasting Total Cholesterol (TC) at Week 12
    End point description
    FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    247
    499
    Units: mg/dL
    arithmetic mean (standard deviation)
        Baseline (n =247, 499)
    209.4 ± 33.84
    210.3 ± 37.97
        Change at Week 12 (n =236, 469)
    -5.9 ± 29.61
    -75.4 ± 46.91
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -69.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -75.2
         upper limit
    -63.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.08

    Secondary: Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (non HDL-C) at Week 12

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    End point title
    Absolute Change From Baseline in Fasting Non High Density Lipoprotein Cholesterol (non HDL-C) at Week 12
    End point description
    FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    247
    499
    Units: mg/dL
    arithmetic mean (standard deviation)
        Baseline (n =247, 499)
    160.2 ± 33.49
    162.1 ± 37.78
        Change at Week 12 (n =236, 469)
    -5.8 ± 29.59
    -77.9 ± 48.28
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -71.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -77.5
         upper limit
    -65.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    3.14

    Secondary: Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12

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    End point title
    Absolute Change From Baseline in Fasting Apolipoprotein B (ApoB) at Week 12
    End point description
    FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    247
    499
    Units: mg/dL
    arithmetic mean (standard deviation)
        Baseline (n =247, 499)
    106.1 ± 20.43
    107.1 ± 23.33
        Change at Week 12 (n =234, 467)
    -1.6 ± 18.09
    -49.8 ± 31.81
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -47.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -51.9
         upper limit
    -43.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.12

    Secondary: Absolute Change From Baseline in Fasting Lipoprotein (A) (Lp[A]) at Week 12

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    End point title
    Absolute Change From Baseline in Fasting Lipoprotein (A) (Lp[A]) at Week 12
    End point description
    FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    247
    499
    Units: mg/dL
    arithmetic mean (standard deviation)
        Baseline (n =247, 499)
    48.5 ± 54.04
    47.3 ± 53.55
        Change at Week 12 (n =235, 469)
    0.1 ± 10.91
    -10.3 ± 17.01
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -10.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -12.5
         upper limit
    -8.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.06

    Secondary: Absolute Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12

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    End point title
    Absolute Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 12
    End point description
    FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    247
    499
    Units: mg/dL
    arithmetic mean (standard deviation)
        Baseline (n =247, 499)
    49.2 ± 13.20
    48.3 ± 11.60
        Change at Week 12 (n =236, 469)
    -0.1 ± 6.75
    2.5 ± 6.64
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    2.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.6
         upper limit
    3.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.52

    Secondary: Absolute Change From Baseline in Ratio of Fasting Total Cholesterol (TC) to High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52

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    End point title
    Absolute Change From Baseline in Ratio of Fasting Total Cholesterol (TC) to High Density Lipoprotein Cholesterol (HDL-C) at Week 12, 24 and 52
    End point description
    FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, 24, 52
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    247
    499
    Units: ratio
    arithmetic mean (standard deviation)
        Baseline (n =247, 499)
    4.6 ± 1.90
    4.6 ± 1.31
        Change at Week 12 (n =236, 469)
    -0.2 ± 1.27
    -1.8 ± 1.29
        Change at Week 24 (n =237, 463)
    -0.2 ± 1.42
    -1.6 ± 1.38
        Change at Week 52 (n =221, 425)
    -0.2 ± 1.62
    -1.5 ± 1.32
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 12: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -1.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.8
         upper limit
    -1.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.08
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 24: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -1.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.6
         upper limit
    -1.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 52: LS mean difference and associated 95% CI were derived from MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -1.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.6
         upper limit
    -1.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.12

    Secondary: Absolute Change From Baseline in Ratio of Fasting Apolipoprotein B (ApoB) to Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52

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    End point title
    Absolute Change From Baseline in Ratio of Fasting Apolipoprotein B (ApoB) to Apolipoprotein A-I (ApoA-I) at Week 12, 24 and 52
    End point description
    FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12, 24, 52
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    247
    499
    Units: ratio
    arithmetic mean (standard deviation)
        Baseline (n =247, 499)
    0.7 ± 0.25
    0.8 ± 0.22
        Change at Week 12 (n =234, 467)
    0.0 ± 0.14
    -0.4 ± 0.25
        Change at Week 24 (n =236, 461)
    -0.0 ± 0.16
    -0.3 ± 0.27
        Change at Week 52 (n =221, 425)
    0.0 ± 0.66
    -0.3 ± 0.25
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 12: LS mean difference and associated 95% confidence interval CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.4
         upper limit
    -0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.02
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 24: LS mean difference and associated 95% confidence interval CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.3
         upper limit
    -0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.02
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 52: LS mean difference and associated 95% confidence interval CI were derived from an MMRM model with fixed effects for treatment group, visit, treatment group*visit interaction, baseline value, baseline value*visit interaction, geographical region and triglyceride subgroup. An unstructured variance covariance matrix was used.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    LS mean difference compared to placebo
    Point estimate
    -0.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.4
         upper limit
    -0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.04

    Secondary: Percentage of Subjects Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 100 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52

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    End point title
    Percentage of Subjects Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 100 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52
    End point description
    FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Week 12, 24, 52
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    247
    499
    Units: percentage of subjects
    number (not applicable)
        Week 12 (n =235, 468)
    10.2
    81.6
        Week 24 (n =236, 461)
    19.9
    75.1
        Week 52 (n =222, 425)
    25.2
    72.7
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 12: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    53.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    32.08
         upper limit
    90.59
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 24: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    17
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    11.15
         upper limit
    26.07
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 52: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    9.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    6.18
         upper limit
    13.48

    Secondary: Percentage of Subjects Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 70 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52

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    End point title
    Percentage of Subjects Achieving Fasting Low Density Lipoprotein Cholesterol (LDL-C) Less Than or Equal to (<=) 70 Milligram per Deciliter (mg/dL) at Week 12, 24 and 52
    End point description
    FAS included all subjects who were randomized. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Week 12, 24, 52
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    247
    499
    Units: percentage of subjects
    number (not applicable)
        Week 12 (n =235, 468)
    1.3
    62.2
        Week 24 (n =236, 461)
    1.7
    60.1
        Week 52 (n 222, 425)
    3.2
    53.4
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 12: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    156.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    48.84
         upper limit
    501.11
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 24: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    110.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    39.77
         upper limit
    308.46
    Statistical analysis title
    Placebo vs PF­-04950615 150 mg
    Statistical analysis description
    Week 52: Odds ratio, associated 95% CI were derived from a logistic regression model with fixed effects for treatment group, baseline value, geographical region and triglyceride subgroup.
    Comparison groups
    Treatment Period: Placebo v Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects included in analysis
    746
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    Odds ratio (OR)
    Point estimate
    43.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    19.52
         upper limit
    96.13

    Secondary: Plasma Concentration Versus Time Summary of PF-04950615

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    End point title
    Plasma Concentration Versus Time Summary of PF-04950615 [1]
    End point description
    Analysis set included all subjects who had taken at least 1 dose of Bococizumab (PF­-04950615) 150 mg. Here, "n" signifies number of subjects who were evaluable at the specified time points.
    End point type
    Secondary
    End point timeframe
    Week 12, 24, 52
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint was planned to be analyzed for Bococizumab 150 mg arm (treatment period) only.
    End point values
    Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    499
    Units: microgram per milliliter
    geometric mean (standard deviation)
        Week 12 (n =456)
    5.37 ± 5.327
        Week 24 (n =448)
    5.28 ± 5.888
        Week 52 (n =418)
    4.01 ± 4.652
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Adverse Events (AEs) Related to Type 1 and 3 Hypersensitivity Reactions and Injection Site Reactions

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    End point title
    Percentage of Subjects With Adverse Events (AEs) Related to Type 1 and 3 Hypersensitivity Reactions and Injection Site Reactions
    End point description
    Type 1 hypersensitivity or allergic reactions were possible in response to any injected protein and included shortness of breath, urticaria, anaphylaxis and angioedema. Type 3 hypersensitivity reactions were similar to Type 1 hypersensitivity reactions but were likely to be delayed from the time of injection and included symptoms such as rash, urticaria, polyarthritis, myalgia’s, polysynovitis, fever and if severe then included glomerulonephritis. Injection site reactions included injection site bruising, discolouration, erythema, haematoma, haemorrhage, nodule, induration, inflammation, mass, pain, paraesthesia, pruritus, swelling, vesicles, warmth, scab and rash. Subjects with type 1 or type 3 hypersensitivity reactions and subjects with injection site reactions were reported in this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline up to end of study (up to 110 weeks)
    End point values
    Treatment Period: Placebo Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    247
    499
    Units: percentage of subjects
    number (not applicable)
        With type 1 or 3 hypersensitivity reactions
    0.0
    0.2
        With injection site reactions
    0.8
    13.4
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Treatment Period

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    End point title
    Percentage of Subjects With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Treatment Period [2]
    End point description
    Percentage of subjects with at least 1 positive ADA titer or 1 positive nAb titer were reported. ADA titer >=6.23 (log 2) unit was considered to be ADA positive and nAb titer >=1.58 (log 2) unit was considered to be nAb positive. Analysis set included all participants who received at least 1 dose of PF-04950615 150 mg. This endpoint was planned not to be analysed for placebo reporting arm. Here, "N" signifies number of subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 58
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint was planned to be analyzed for Bococizumab 150 mg arm (treatment period) only.
    End point values
    Treatment Period: Bococizumab (PF­-04950615) 150 mg
    Number of subjects analysed
    491
    Units: Percentage of subjects
    number (not applicable)
        Baseline up to Week 58: ADA positive
    54.8
        Baseline up to Week 58: nAb positive
    37.9
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period

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    End point title
    Percentage of Subjects With Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (nAb): Extension Period
    End point description
    Percentage of subjects with at least 1 positive ADA titer or 1 positive nAb titer were reported. ADA titer >=6.23 (log2) unit was considered to be ADA positive and nAb titer >=1.58 (log2) unit was considered to be nAb positive. All subjects who consented for extension period. This endpoint was planned not to be analyzed for reporting arms Placebo (Extension period) and Bococizumab ADA negative (Extension period). Here, "n" signifies number of participants who were evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    Week 58 (follow-up), Week 71, Week 84, Week 97, Week 110
    End point values
    Extension Period: Bococizumab ADA positive
    Number of subjects analysed
    33
    Units: percentage of subjects
    number (not applicable)
        Week 58 (follow up): ADA positive (n =33)
    100.0
        Week 58 (follow up): nAB positive (n =33)
    60.6
        Week 71: ADA positive (n =31)
    87.1
        Week 71: nAb positive (n =31)
    35.5
        Week 84: ADA positive (n =28)
    82.1
        Week 84: nAb positive (n =28)
    25.0
        Week 97: ADA postive (n =22)
    86.4
        Week 97: nAb positive (n =22)
    18.2
        Week 110: ADA positive (n =17)
    100.0
        Week 110: nAb positive (n =17)
    11.8
    No statistical analyses for this end point

    Secondary: Number of Subjects Who Changed Concomitant Medication During Extension Period

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    End point title
    Number of Subjects Who Changed Concomitant Medication During Extension Period
    End point description
    In this endpoint, total number of subjects who changed their lipid-lowering medications or added a monoclonal antibody medication during the extension period were reported. All subjects who consented for extension period.
    End point type
    Secondary
    End point timeframe
    Week 58 follow-up to Week 110
    End point values
    Extension Period: Placebo Extension Period: Bococizumab ADA positive Extension Period: Bococizumab ADA negative
    Number of subjects analysed
    44
    33
    56
    Units: subjects
    2
    4
    3
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 58 (follow up), 71, 84, 97 and 110: Extension Period

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    End point title
    Percent Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 58 (follow up), 71, 84, 97 and 110: Extension Period
    End point description
    All subject who consented for extension period. This endpoint was planned not to be analyzed for reporting arms: Placebo (Extension Period) and Bococizumab ADA negative (Extension Period).
    End point type
    Secondary
    End point timeframe
    Baseline, Week 58 (follow up), 71, 84, 97, 110
    End point values
    Extension Period: Bococizumab ADA positive
    Number of subjects analysed
    33
    Units: percent change
    arithmetic mean (standard deviation)
        Week 58 (follow up)
    6.7 ± 27.70
        Week 71
    8.7 ± 34.83
        Week 84
    7.0 ± 30.34
        Week 97
    2.6 ± 31.43
        Week 110
    15.5 ± 36.17
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    For SAEs: Baseline up to Week 110 and for other AEs: Baseline up to Week 58
    Adverse event reporting additional description
    Event may be serious in 1 and nonserious in other subject or 1 subject may have experienced both serious and nonserious AE. Subjects evaluable:treatment period: subjects who received at least 1 dose of study drug;extension period:subjects who consented for extension period.Nonserious AEs were not collected for extension period.99999=not available.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Subjects received placebo matched to Bococizumab (PF-04950615) subcutaneous injection once every 2 weeks up to Week 52. Subjects were followed up to Week 58.

    Reporting group title
    Bococizumab (PF­-04950615) 150 mg
    Reporting group description
    Subjects received Bococizumab (PF­04950615) 150 mg subcutaneous injection once every 2 weeks up to Week 52. Sujects were followed up to Week 58.

    Reporting group title
    Extension Period: Placebo
    Reporting group description
    Subjects randomized to Placebo arm in treatment period and consented for extension period after Week 58 follow-up visit, were followed for SAEs and concomitant medications up to Week 110.‌

    Reporting group title
    Extension Period: Bococizumab ADA positive
    Reporting group description
    Subjects randomized to Bococizumab in treatment period were classified as either ADA positive or ADA negative based on their ADA assessment at Week 58 follow-up visit. In extension period, subjects who were ADA positive and consented for extension period were assessed for ADA and LDL-C direct measurement until ADA titers were no longer detectable or had returned to baseline titer (less than or equal to 1.58 log2 units above a positive baseline titer) or until Week 110 along with SAEs and concomitant medication, from Week 58 follow up visit to Week 110.

    Reporting group title
    Extension Period: Bococizumab ADA negative
    Reporting group description
    Subjects randomized to Bococizumab in treatment period were classified as either ADA positive or ADA negative based on their Week 58 follow-up ADA assessment. Subjects who were ADA negative and consented for extension period were followed for SAEs and concomitant medication, from Week 58 follow up visit to Week 110.

    Serious adverse events
    Placebo Bococizumab (PF­-04950615) 150 mg Extension Period: Placebo Extension Period: Bococizumab ADA positive Extension Period: Bococizumab ADA negative
    Total subjects affected by serious adverse events
         subjects affected / exposed
    32 / 247 (12.96%)
    44 / 499 (8.82%)
    2 / 44 (4.55%)
    0 / 33 (0.00%)
    1 / 56 (1.79%)
         number of deaths (all causes)
    2
    2
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery dissection
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bone cancer
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer recurrent
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-small cell lung cancer
         subjects affected / exposed
    1 / 247 (0.40%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin cancer
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsil cancer
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disease progression
    alternative dictionary used: MedDRA v20.0J
         subjects affected / exposed
    0 / 247 (0.00%)
    0 / 499 (0.00%)
    1 / 44 (2.27%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    POSSIBLE SEIZURE DISORDER SECONDARY TO AMPHETAMINE ABUSE
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 247 (0.40%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Complication associated with device
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    1 / 247 (0.40%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 247 (0.00%)
    5 / 499 (1.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular stent occlusion
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression suicidal
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paranoia
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric decompensation
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicidal behaviour
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Arterial injury
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    2 / 247 (0.81%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 247 (0.40%)
    3 / 499 (0.60%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    2 / 247 (0.81%)
    4 / 499 (0.80%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 247 (0.00%)
    2 / 499 (0.40%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    2 / 247 (0.81%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery occlusion
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    3 / 247 (1.21%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus bradycardia
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation1
    alternative dictionary used: MedDRA 20.0J
         subjects affected / exposed
    0 / 247 (0.00%)
    0 / 499 (0.00%)
    1 / 44 (2.27%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
    alternative dictionary used: MedDRA 20.0J
         subjects affected / exposed
    0 / 247 (0.00%)
    0 / 499 (0.00%)
    1 / 44 (2.27%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 247 (0.00%)
    2 / 499 (0.40%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest pain
    alternative dictionary used: MedDRA v20.0J
         subjects affected / exposed
    0 / 247 (0.00%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
    alternative dictionary used: MedDRA v 20.0J
         subjects affected / exposed
    0 / 247 (0.00%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral haematoma
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 247 (0.00%)
    3 / 499 (0.60%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Miller Fisher syndrome
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radiculopathy
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 247 (0.40%)
    2 / 499 (0.40%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Sudden hearing loss
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal hernia
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    2 / 247 (0.81%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophageal perforation
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 247 (0.40%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Diabetic foot
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bursitis
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spondyloarthropathy
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendonitis
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypoglycaemia
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Arthritis bacterial
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infected skin ulcer
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Klebsiella sepsis
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 247 (0.40%)
    2 / 499 (0.40%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 247 (0.40%)
    0 / 499 (0.00%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 247 (0.00%)
    1 / 499 (0.20%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Placebo Bococizumab (PF­-04950615) 150 mg Extension Period: Placebo Extension Period: Bococizumab ADA positive Extension Period: Bococizumab ADA negative
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    29 / 247 (11.74%)
    97 / 499 (19.44%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
    General disorders and administration site conditions
    Injection site reaction
    Additional description: For extension Period, NSAEs were not collected and hence actual population exposed is "0". Current presentation is a resolution of database limitation.
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 247 (0.81%)
    67 / 499 (13.43%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    2
    328
    0
    0
    0
    Infections and infestations
    Nasopharyngitis
    Additional description: For extension Period, NSAEs were not collected and hence actual population exposed is "0". Current presentation is a resolution of database limitation.
    alternative assessment type: Systematic
         subjects affected / exposed
    14 / 247 (5.67%)
    17 / 499 (3.41%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    19
    18
    0
    0
    0
    Upper respiratory tract infection
    Additional description: For extension Period, NSAEs were not collected and hence actual population exposed is "0". Current presentation is a resolution of database limitation.
    alternative assessment type: Systematic
         subjects affected / exposed
    14 / 247 (5.67%)
    18 / 499 (3.61%)
    0 / 44 (0.00%)
    0 / 33 (0.00%)
    0 / 56 (0.00%)
         occurrences all number
    16
    21
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    29 Jul 2014
    Study follow-up period was reduced from 8 to 6 weeks.
    17 May 2016
    For US sites, addition of a substudy to provide additional follow up of subjects who were ADA positive at the last study visit.
    07 Jul 2016
    For US sites, addition of a substudy that provides additional follow-up of subjects who were ADA positive and information on use of concomitant medication, LDL-C,and to not discontinue subjects who start treatment with a PCSK9 inhibitor.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    The status of studies in GB is no longer updated from 1.1.2021
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